An L-arginine-nitric oxide-cyclic guanosine monophosphate system exists in the uterus and inhibits contractility during pregnancy

Abstract

Objective: Nitric oxide is synthesized from L-arginine and it causes relaxation of smooth muscle by elevating cyclic guanosine monophosphate levels. We hypothesized that an L-arginine-nitric oxide-cGMP system is present in the uterus and modulates contractility.

Study design: Isometric tension of the uterus was measured in vitro from pregnant rats in response to various agents that modulate nitric oxide-cyclic guanosine monophosphate production or action.

Results: Major findings are as follows: (1) The substrate and a donor of nitric oxide produced uterine relaxation; (2) inhibitors of the nitric oxide-cyclic guanosine monophosphate pathway blocked the relaxation responses; (3) nitric oxide synthase was localized to several uterine cell types; (4) nitric oxide was produced by the uterus during periods when L-arginine was consumed and citrulline levels increased; (5) effects of nitric oxide substrate on relaxation were mimicked by cyclic guanosine monophosphate; (6) nitric oxide-cyclic guanosine monophosphate responses were decreased during delivery; (7) L-arginine responses were increased by progesterone, and antiprogesterone treatment decreased cyclic guanosine monophosphate-induced relaxations.

Conclusion: An L-arginine-nitric oxide-cyclic guanosine monophosphate system is present in the uterus and it may regulate relaxation during pregnancy. The inhibitory action of L-arginine and 8-bromo-cyclic guanosine monophosphate was considerably lower during delivery and post partum, indicating that the nitric oxide system may contribute to the maintenance of uterine quiescence during pregnancy, when progesterone levels are elevated, but not during delivery.